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(there is a nice confusion in the literature some authors use simply adjuvants some distinct clearly delivery
Antigen(s) against which adaptive
immune
responses are elicited
systems and
potentiators)
Delivery systems to ensure that the vaccine antigen is delivered to the right
place at the right time. It means the role of a delivery system is to enhance
the amount of antigen reaching the cells responsible for immune response
induction.
The lipopolisaccharide (LPS) component of Gramnegative bacteria has been shown to act as a potent
immune potentiator however, the profound toxicity
and pyrogenicity of LPS prevents its use in humans.
Currently
In
As
Immunological background I.
AF03
The slow process of adjuvant discovery. Alum was the first adjuvant to
be licensed in the 1920s and is still the only adjuvant approved for
human use in the USA. The squalene-based oil-in-water emulsion MF59
was first licensed in Europe for a flu vaccine (FLUAD) in 1997. The
LPS analog monophosphoryl lipid A (MPL) formulated with alum (AS04)
was first approved for an HBV vaccine (Fendrix) in Europe in 2005.
The oil-in-water emulsion AS03 was approved for a pandemic flu
vaccine (Prepandrix) in 2008. AF03 Humenza in 2009.
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Alum I.
Aluminium
Although
Moreover,
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Proposed mechanisms of action of alum in vitro and in vivo and their possible contributions to
adjuvanticity.
In vitro, alum complexed with antigen increases antigen uptake by APC. In addition, alum
induces direct activation of Nlrp3 (Nalp3) inflammasome complex and synergizes with
LPS stimulation of TLR4 for the secretion pro-inflammatory cytokines such as IL-1b, IL18 and IL-33.
In vivo, alum induces necrosis in unidentified target cells resulting in production of uric acid,
which has the potential to stimulate Nlrp3. Alum also stimulates local recruitment of APC
and migration of APC to the draining lymph nodes. It has been proposed that alum may
also enhance local antigen persistency ("depot" effect). The contribution of all these
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activities to alum adjuvanticity and the requirement of Nlrp3 are not yet fully understood.